Chapter 7 - Cannabis: Effects and Consequences

Consequences of chronic use

 

Most of the works consulted in pharmacology, toxicology and psychiatry speak of chronic effects. For our part, we prefer to speak of consequences resulting from chronic use. There are two reasons for this. First of all, because these consequences result not so much from the substance itself as from the way it is used. Therefore we are not dealing with the effects of the substance, but rather with the consequences that may arise from repeated, or even heavy, use. The second reason is that, as we saw in Chapter 6, chronic cannabis users account for a small fraction (often less than 10%) of lifetime users of cannabis. As a result, the consequences in question in this section concern this small portion of the population of users and not the substance itself.

We feel this distinction is fundamental because it is common, at all levels of public discussion – whether involving politicians, the public at large, or experts – to blame the substance – here cannabis, there alcohol or medications, even other illicit drugs–when in fact we must learn to distinguish between patterns and methods of use. By that we mean at-risk behaviour, which varies with the substance of course, and which does not depend solely on the intrinsic properties of the substance, but stems, in an overall approach, from the relationship between the substance and its place in society (integrated or not) from the individual’s characteristics, and from the society in which the substance is used.[1][29] Of course by that it should be clear that we consider as separate, for cannabis as for alcohol, use, at-risk use and heavy use (or abuse)[2][30], and that we reject the equivalency often made between use and abuse where any form of use is perceived as abuse. At the same time, we are aware of the vagueness that continues to surround these various types of behaviour – or practices – and that there is no clearly defined boundary, even less a universal boundary, between use, harmful use and dependence. For the purposes of this chapter, the consequences in question in the following three sections refer, without being more specific, to chronic use (which then includes at-risk and heavy use).

 

Physiological consequences of chronic use

The main physiological consequences of the chronic use of cannabis dealt with in scientific literature concern the respiratory system and the carcinogenicity of cannabis, the immune system, the endocrine system and reproductive functions and, to a lesser degree, the cardiovascular system.

 

Consequences for the respiratory system

Except for the nicotine in tobacco and the cannabinoids in cannabis, the smoke of these two products shares common irritating, even carcinogenic, properties. Although not recent, a comparative analysis of these products has shown that the concentration of certain strongly carcinogenic ingredients such as benzopyrene and benzanthracene is higher in cannabis smoke than tobacco smoke.[3][31] A more recent study cited by INSERM confirms this higher concentration of benzopyrene: 2.9 micrograms/100 joints compared to 1.7 for 100 cigarettes.[4][32] Of course, it will be argued that tobacco users generally smoke many more cigarettes a day than even chronic users of marijuana, that it is the total volume of toxic substances inhaled over time that counts, and that it can be difficult to distinguish the effects of cannabis from those of tobacco since joints often contain both products and users of cannabis are also often tobacco smokers.[5][33]

However we note other worrisome characteristics with respect to the potential effects on the respiratory tract of smoking cannabis. First of all, the concentration of benzopyrene in marijuana tar is 70% higher than that in the same weight of tobacco tar. Furthermore, an equal product weight of cannabis provides up to 4 times more tar than a strong tobacco. According to a study cited by INSERM, tar from a joint varies between 40 and 56 mg/cigarette whereas the allowable dose for a European tobacco cigarette is 12 mg.[6][34] In addition, a marijuana cigarette is generally smoked much more completely than a tobacco cigarette, inhalation – an important part of the ritual – is deeper and the smoke is held in the lungs longer and the combustion temperature of cannabis is higher than that of tobacco. Consequently, the percentage of tar deposited in the lungs is higher after smoking cannabis (> 80%) than after inhaling tobacco (64%) and the deposits are even greater for cannabis with a lower concentration of THC, probably because smokers draw on the joint more.[7][35]

According to INSERM’s report, chronic use of cannabis “results in unquestionable bronchial disorders (…) chronic bronchitis with a chronic cough, expectorations and a sibilant rale”[8][36] [translation], a conclusion shared by the Institute of Medicine in the United States in its recent report on marijuana[9][37] as well as by the WHO.[10][38] Moreover, macrophages (cells that attack foreign bodies) in the pulmonary alveoli seem to lose their ability to neutralize bacteria when exposed to cannabis smoke, hence the greater susceptibility of the bronchi and lungs to bacterial infections. According to some authors, in theory, a cannabis cigarette could cause as much damage as 4 to 10 tobacco cigarettes.[11][39] This data on the reduced ability of alveolar macrophages to destroy bacteria also suggests that cannabis could have an immunosuppressive action that decreases the ability of the organism, here the lungs, to fight carcinogenic cells.

The work of Tashkin in particular, but also of other researchers, is not as confirmatory on the effects of cannabis on the respiratory tract. Thus a recent study by Tashkin on heavy cannabis smokers showed that there was no decrease in the forced expiratory volume in one second to vital capacity ratio, even for those who smoked 3 joints a day, compared to tobacco smokers who registered a significant decrease.[12][40] Tashkin’s team also questioned the development of emphysema in cannabis users and bronchiole obstruction.[13][41] Similarly, a study by the Kaiser Permanent Medical Care Program revealed that daily cannabis users who did not use tobacco were hardly more likely than non-smokers (36% vs. 33%) to consult for colds, the flu and bronchitis.[14][42] We also note that to date, studies are contradictory about the additivity of the effects of tobacco and cannabis.

 

Carcinogenic potential

With respect to the carcinogenic potential of cannabis, there is a distinction between the carcinogenic effects of cannabis smoke – a potential source of lung cancer in particular – and the mutagenic effects of THC on cells. According to the majority of authors, THC itself does not seem to be carcinogenic.[15][43] However, cannabis smoke, like tobacco smoke, does seem to be able to increase the incidence of cancerous tumors.

The work of Fliegel[16][44] indicates that the histological changes that are considered the precursors of carcinomata are present in chronic smokers of cannabis. This data is also supported by clinical cases of cancers of the upper aerodigestive tract in young adult cannabis smokers. These cancers are types rarely observed in young subjects. Namely:

··               Thirteen cases of brain and neck cancer in young adults under the age of forty, eleven of whom were daily cannabis smokers;[17][45]

··               Ten cases of cancers of the upper respiratory tract in young adults under the age of forty, seven of whom were probable regular users of cannabis;[18][46] and

··               Two cases of carcinoma of the tongue in men between 37 and 52 years of age for whom the only common risk factor was the regular and daily use of cannabis.[19][47]

 

We note first of all the small number of cases, especially when compared to the large number of cannabis users. These clinical cases also present a certain number of important limitations: none compares the prevalence of cancer with a control group or evaluates the use of cannabis in a standardized way. Interpretation is also limited by the fact that the patients also smoked tobacco and drank alcohol.

The data available seems to indicate that the consequences of chronic and intense cannabis use (several joints per day for several years) are similar to those of cigarettes in terms of carcinogenic risks for the respiratory tract as well as the mouth, the tongue and the esophagus.[20][48] THC is generally considered to alter the functions of certain cells, namely lymphocytes, macrophages and polymorphonuclear cells, especially in in vitro models. However conducting controlled studies is largely recognized as a research priority in this field.[21][49]

 

Consequences for the immune system

Apart from the possible consequences for the respiratory tract defense system essentially caused by smoke, there is no conclusive data regarding the effects of cannabis on the immune system. Some studies on rodents show that high levels of cannabinoids, including THC, alter cellular immunity. In some cases, the experimental activity of cannabinoids is immunosuppressive and in others it is stimulating. These variations depend on experimental factors such as the concentration of the substance, the time and duration of administration, and the type of cell function studied. Very little work has been done on humans. According to the WHO report, if it is clear that cannabinoids have immunomodulating effects, it is also clear that the immune system is resistant to this substance. Several of the effects are relatively minimal and completely reversible, and are only experienced at higher doses than those required for the drug’s psychoactive effect in humans. Lastly, still according to the WHO report, even with respect to the immunomodulating effects of cannabis smoke, the studies are not conclusive and it is hard to compare the doses used in experiments with animals to the doses used by humans. The report concludes that rigorous studies on this question are necessary.[22][50]

 

Consequences for the endocrine system and reproduction

Endocrine abnormalities are well documented in animals. In the male rat, decreased testosterone secretion with testicular atrophy, impaired production, mobility and viability of sperm, and changes in sexual behaviour have been noted with high doses. The ovulatory cycle of the female is altered. In humans, the results are contradictory, in particular because findings are not constant from one study to another, but also because similar changes occur following the absorption of prescription drugs. Furthermore, the changes observed are often borderline normal and their clinical consequences remain controversial.[23][51]

With respect to reproduction, the fact that the active ingredients in cannabis cross the placental barrier is well established. Nevertheless, the question of the potential effects of cannabis on the feotus is far from resolved, especially since the studies are methodologically poor. Thus, when studying pregnant women who are cannabis users, the women often come from low socio-economic backgrounds – and we know that socio-economic level is a determining factor in the size and weight of babies – and it is difficult to isolate the effect of other factors, including the use of tobacco and alcohol – which we know are risk factors for premature birth, lower weight and smaller size. In fact, studies on occasional cannabis smokers do not show any significant difference with respect to non-smokers. All in all, most studies did not observe any significant differences.[24][52] Nevertheless, reports from the WHO and the collective expertise of INSERM conclude that, despite methodological difficulties, there is reasonable evidence that cannabis use during pregnancy harms fetal development, in particular restricted growth and behavioural abnormalities, but that these abnormalities are rather minor.[25][53]

As for the neonatal consequences of cannabis use by mothers during pregnancy, longitudinal studies on cohorts of children conducted in Ottawa since 1978 by psychologist Peter Fried’s team[26][54] are not conclusive. All the measurements taken reveal more similarities than differences between the children of smokers and non-smokers. And when differences are observed, they are minor and it is impossible to dissociate the effects of the various substances, tobacco and alcohol in particular. Lastly, these studies involve a small sample of children and generalizations cannot be drawn from them. Another longitudinal study, reported by INSERM, involving 636 subjects, concluded [translation] “there is a significant relationship between behavioural problems at age 10 and prenatal exposure to cannabis.” However the report from INSERM also notes that [translation] “if the results from these two studies seem to converge well (…) we must remember nevertheless that the postnatal environment can play an important role in the continuation of behavioural abnormalities.”[27][55]

 

Consequences for the cardiovascular system

Chronic use of cannabis may lead to cardiovascular complications for predisposed individuals. In fact, the use of significant quantities can slow the heart rate. Also, cannabis can have similar effects to those of tobacco on heart function by increasing the muscle workload. Furthermore, some studies point out the role that the carbon monoxide found in cannabis smoke plays in the risk of cardiovascular complications.